Improvements in hospice utilization among patients with advanced-stage lung cancer in an integrated health care system.

BACKGROUND: Hospice, a patient-centered care system for those with limited life expectancy, is important for enhancing quality of life and is understudied in integrated health care systems. METHODS: This was a retrospective cohort study of 21,860 decedents with advanced-stage lung cancer diagnosed from January 2007 to June 2013 in the national US Veterans Affairs Health Care System. Trends over time, geographic regional variability, and patient and tumor characteristics associated with hospice use and the timing of enrollment were examined. Multivariable logistic regression and Cox proportional hazards modeling were used. RESULTS: From 2007 to 2013, 70.3% of decedents with advanced-stage lung cancer were enrolled in hospice. Among patients in hospice, 52.9% were enrolled in the last month of life, and 14.7% were enrolled in the last 3 days of life. Hospice enrollment increased (adjusted odds ratio [AOR], 1.07; P < .001), whereas the mean time from the cancer diagnosis to hospice enrollment decreased by 65 days (relative decrease, 32%; adjusted hazard ratio, 1.04; P < .001). Relative decreases in late hospice enrollment were observed in the last month (7%; AOR, 0.98; P = .04) and last 3 days of life (26%; AOR, 0.95; P < .001). The Southeast region of the United States had both the highest rate of hospice enrollment and the lowest rate of late enrollment. Patient sociodemographic and lung cancer characteristics were associated with hospice enrollment. CONCLUSIONS: Among patients with advanced-stage lung cancer in the Veterans Affairs Health Care System, overall and earlier hospice enrollment increased over time. Considerable regional variability in hospice enrollment and the persistence of late enrollment suggests opportunities for improvement in end-of-life care. Cancer 2018;124:426-33. © 2017 American Cancer Society.

Lower Urinary Tract Symptoms and Risk of Nonspine Fractures among Older Community Dwelling U.S. Men.

PURPOSE: Among older men, moderate and severe lower urinary tract symptoms are associated with increased fall risk compared to mild lower urinary tract symptoms. Falls are a major risk factor for fractures. Therefore, we assessed associations of lower urinary tract symptoms with fracture risk in community dwelling U.S. men age 65 years or older. MATERIALS AND METHODS: We conducted a prospective study in the MrOS (Osteoporotic Fractures in Men Study) cohort. Men were enrolled at 6 U.S. sites. The AUA-SI, lower urinary tract symptoms medication use, fracture risk factors and potential confounders were recorded at baseline and every 2 years thereafter for 4 assessments. Lower urinary tract symptom severity was categorized from the AUA-SI as mild (0 to 7 points), moderate (8 to 19 points) or severe (20 or more points). Associations of lower urinary tract symptom severity with fracture rate were estimated with HRs and 95% CIs from extended proportional hazards regression. RESULTS: Among 5,989 men with baseline AUA-SI score and hip bone mineral density measures, 745 incident nonspine fractures occurred during 43,807 person-years of followup. In a multivariable model adjusted for age, enrollment site, baseline hip bone mineral density, falls in the last year and prevalent fracture before baseline, there were no significant associations of moderate (HR 0.9, 95% CI 0.8-1.1) or severe (HR 1.0, 95% CI 0.8-1.3) lower urinary tract symptoms with fracture risk. None of the individual lower urinary tract symptoms assessed on the AUA-SI, including nocturia and urgency, was associated with increased fracture risk. CONCLUSIONS: In this cohort of older U.S. men, lower urinary tract symptoms were not independently associated with fracture risk.

Two Years in the Life of a University Hospital Tobacco Cessation Service: Recommendations for Improving the Quality of Referrals.

BACKGROUND: Hospitalization, when patients may be more receptive to quitting, provides an opportunity to provide tobacco cessation services for patients who otherwise might not seek help. Although specialized tobacco cessation services are shown to be effective if evidence-based treatment, including follow-up, is completed, resources are limited and guidelines are needed, and few smokers complete all treatment steps. Experience drawn from an analysis of two-year implementation data from the Oregon Health & Science University (OHSU) Tobacco Cessation Consult Service is presented. METHODS: Data for 5,827 smokers discharged from OHSU University hospital between January 2011 and December 2012 were analyzed to determine patient characteristics and identify predictors of completing each of four treatment steps: consult ordered, consult completed, follow-up arranged, and follow-up completed. RESULTS: Smokers were younger and male (p<0.0001) and significantly different with respect to insurance class, admission type, history of mental disorders, primary discharge diagnoses, and length of stay (p<0.0001) than nonsmokers. Predictors of having a tobacco consult order were admission for elective medical procedures; orders for medications to treat withdrawal; history of mental health/substance use disorders; primary diagnoses of cardiovascular, endocrine, gastrointestinal, or pulmonary disease; and longer hospitalizations. Smokers admitted through the emergency department had the lowest rates of follow-up completion and abstinence. Admission for an elective surgery was the only predictor of completing all treatment steps through followup (p≤0.05). CONCLUSIONS: This study adds important information about how hospitalized smokers respond to each step of tobacco treatment in a real-world setting and offers strategies for improving referrals.

Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in women with preterm labor and intact membranes.

OBJECTIVE: Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). STUDY DESIGN: This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). RESULTS: MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. CONCLUSION: High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.

Travel-associated antimicrobial drug-resistant nontyphoidal Salmonellae, 2004-2009.

To evaluate trends in and risk factors for acquisition of antimicrobial-drug resistant nontyphoidal Salmonella infections, we searched Oregon surveillance data for 2004-2009 for all culture-confirmed cases of salmonellosis. We defined clinically important resistance (CIR) as decreased susceptibility to ampicillin, ceftriaxone, ciprofloxacin, gentamicin, or trimethoprim/sulfamethoxazole. Of 2,153 cases, 2,127 (99%) nontyphoidal Salmonella isolates were obtained from a specific source (e.g., feces, urine, blood, or other normally sterile tissue) and had been tested for drug susceptibility. Among these, 347 (16%) isolates had CIR. The odds of acquiring CIR infection significantly increased each year. Hospitalization was more likely for patients with than without CIR infections. Among patients with isolates that had been tested, we analyzed data from 1,813 (84%) who were interviewed. Travel to eastern or Southeast Asia was associated with increased CIR. Isolates associated with outbreaks were less likely to have CIR. Future surveillance activities should evaluate resistance with respect to international travel.

Proteomic changes induced by longevity-promoting interventions in mice.

Using mouse models and high-throughput proteomics, we conducted an in-depth analysis of the proteome changes induced in response to seven interventions known to increase mouse lifespan. This included two genetic mutations, a growth hormone receptor knockout (GHRKO mice) and a mutation in the Pit-1 locus (Snell dwarf mice), four drug treatments (rapamycin, acarbose, canagliflozin, and 17α-estradiol), and caloric restriction. Each of the interventions studied induced variable changes in the concentrations of proteins across liver, kidney, and gastrocnemius muscle tissue samples, with the strongest responses in the liver and limited concordance in protein responses across tissues. To the extent that these interventions promote longevity through common biological mechanisms, we anticipated that proteins associated with longevity could be identified by characterizing shared responses across all or multiple interventions. Many of the proteome alterations induced by each intervention were distinct, potentially implicating a variety of biological pathways as being related to lifespan extension. While we found no protein that was affected similarly by every intervention, we identified a set of proteins that responded to multiple interventions. These proteins were functionally diverse but tended to be involved in peroxisomal oxidation and metabolism of fatty acids. These results provide candidate proteins and biological mechanisms related to enhancing longevity that can inform research on therapeutic approaches to promote healthy aging.

Trends and correlates of child passenger restraint use in 6 Northwest tribes: the Native Children Always Ride Safe (Native CARS) project.

OBJECTIVES: We compared proportions of children properly restrained in vehicles in 6 Northwest American Indian tribes in 2003 and 2009, and evaluated risks for improper restraint. METHODS: During spring 2009 we conducted a vehicle observation survey in Oregon, Washington, and Idaho tribal communities. We estimated the proportions of children riding properly restrained and evaluated correlates of improper restraint via log-binomial regression models for clustered data. RESULTS: We observed 1853 children aged 12 years and younger in 1207 vehicles; 49% rode properly restrained. More children aged 8 years and younger rode properly restrained in 2009 than 2003 (51% vs 29%; P < .001). Older booster seat-eligible children were least likely to ride properly restrained in 2009 (25%). American Indian children were more likely to ride improperly restrained than nonnative children in the same communities. Other risk factors included riding with an unrestrained or nonparent driver, riding where child passenger restraint laws were weaker than national guidelines, and taking a short trip. CONCLUSIONS: Although proper restraint has increased, it remains low. Tribe-initiated interventions to improve child passenger restraint use are under way.

The association between insurance status and cervical cancer screening in community health centers: exploring the potential of electronic health records for population-level surveillance, 2008-2010.

INTRODUCTION: Cervical cancer incidence and mortality rates in the United States have decreased 67% over the past 3 decades, a reduction mainly attributed to widespread use of the Papanicolaou (Pap) test for cervical cancer screening. In the general population, receipt of cervical cancer screening is positively associated with having health insurance. Less is known about the role insurance plays among women seeking care in community health centers, where screening services are available regardless of insurance status. The objective of our study was to assess the association between cervical cancer screening and insurance status in Oregon and California community health centers by using data from electronic health records. METHODS: We used bilevel log-binomial regression models to estimate prevalence ratios and 95% confidence intervals for receipt of a Pap test by insurance status, adjusted for patient-level demographic factors and a clinic-level random effect. RESULTS: Insurance status was a significant predictor of cervical cancer screening, but the effect varied by race/ethnicity and age. In our study uninsured non-Hispanic white women were less likely to receive a Pap test than were uninsured women of other races. Young, uninsured Hispanic women were more likely to receive a Pap test than were young, fully insured Hispanic women, a finding not previously reported. CONCLUSION: Electronic health records enable population-level surveillance in community health centers and can reveal factors influencing use of preventive services. Although community health centers provide cervical cancer screening regardless of insurance status, disparities persist in the association between insurance status and receipt of Pap tests. In our study, after adjusting for demographic factors, being continuously insured throughout the study period improved the likelihood of receiving a Pap test for many women.

The Instrumented Stand and Walk (ISAW) test to predict falls in older men.

Objective measures of balance and gait have the potential to improve prediction of future fallers because balance and gait impairments are common precursors. We used the Instrumented Stand and Walk Test (ISAW) with wearable, inertial sensors to maximize the domains of balance and gait evaluated in a short test. We hypothesized that ISAW objective measures across a variety of gait and balance domains would improve fall prediction beyond history of falls and better than gait speed or dual-task cost on gait-speed. We recruited 214 high-functioning older men (mean 82 years), of whom 91 participants (42.5%) had one or more falls in the 12 months following the ISAW test. The ISAW test involved 30 s of stance followed by a 7-m walk, turn, and return. We examined regression models for falling using 17 ISAW metrics, with and without age and fall history, and characterize top-performing models by AUC and metrics included. The ISAW test improved distinguishing between future fallers and non-fallers compared to age and history of falls, alone (AUC improved from 0.69 to 0.75). Models with 1 ISAW metric usually included a postural sway measure, models with 2 ISAW measures included a turning measure, models with 3 ISAW measures included a gait variability measure, and models with 4 or 5 measures added a gait initiation measure. Gait speed and dual-task cost did not distinguish between fallers and non-fallers in this high-functioning cohort. The best fall-prediction models support the notion that older people may fall due to a variety of balance and gait impairments.

Experimental design considerations for studies of human tear proteins.

PURPOSE: Human tears contain abundant, diverse sets of proteins that may serve as biomarkers of ocular surface health. There is a need for reproducible methods that consider multiple factors influencing the tear proteome, in addition to the variable of interest. Here we examined a workflow for proteomic analysis of tear proteins without the need to pool tear samples from multiple individuals, thus allowing for analyses based on individual factors, and increasing opportunities for protein biomarker discovery. METHODS: Tears were collected by Schirmer strip following topical ocular anesthetic application then individually stored at -80 °C prior to processing for proteomics. Tear proteins were extracted from Schirmer strips, digested using suspension trapping spin columns (S-Trap), and labeled with high multiplicity tandem mass tags (TMT). Peptide digests were then extensively fractionated by two-dimensional chromatography and analyzed by mass spectrometry to identify and measure changes in protein abundance in each sample. Analysis of select samples was performed to test protocols and to compare the impact of clinically relevant parameters. To facilitate comparison of separate TMT experiments, common pool samples were included in each TMT instrument run and internal reference scaling (IRS) was performed. RESULTS: Differences in subsets of tear proteins were noted for: geographic site of tear collection, contact lens use, and differences in tear fluid volume among individuals. CONCLUSION: These findings demonstrate that proteomic analysis of human tear proteins can be performed without the need to pool samples, and that development of analytic workflows must consider factors that may affect outcomes in studies focused on diverse clinical samples.

Melanoma literacy among the general population of three western US states.

Melanoma is a significant cause of cancer death, despite being detectable without specialized or invasive technologies. Understanding barriers to preventive behaviors such as skin self-examination (SSE) could help to define interventions for increasing the frequency of early detection. To determine melanoma knowledge and beliefs across three high-incidence US states, 15,000 surveys were sent to a population-representative sample. We aimed to assess (1) melanoma literacy (i.e., knowledge about melanoma risks, attitudes, and preventive behaviors) and (2) self-reported SSE and its association with melanoma literacy, self-efficacy, and belief in the benefits of SSE. Of 2326 respondents, only 21.2% provided responses indicating high knowledge of melanoma, and 62.8% reported performing an SSE at any time in their lives. Only 38.3% and 7.3% reported being "fairly" or "very" confident about doing SSE, respectively. SSE performance among respondents was most strongly associated with higher melanoma knowledge, higher self-efficacy, and personal history of melanoma. Melanoma literacy among survey respondents was modest, with greater literacy associated with a higher likelihood of reported preventive behavior. This assessment establishes a baseline and provides guidance for public health campaigns designed to increase prevention and early detection of this lethal cancer.

Relationships Between Sensorimotor Inhibition and Mobility in Older Adults With and Without Parkinson's Disease.

BACKGROUND: Reduced cortical sensorimotor inhibition is associated with mobility and cognitive impairments in people with Parkinson's disease (PD) and older adults (OAs). However, there is a lack of clarity regarding the relationships among sensorimotor, cognitive, and mobility impairments. The purpose of this study was to determine how cortical sensorimotor inhibition relates to impairments in mobility and cognition in people with PD and OAs. METHOD: Cortical sensorimotor inhibition was characterized with short-latency afferent inhibition (SAI) in 81 people with PD and 69 OAs. Six inertial sensors recorded single- and dual-task gait and postural sway characteristics during a 2-minute walk and a 1-minute quiet stance. Cognition was assessed across the memory, visuospatial, executive function, attention, and language domains. RESULTS: SAI was significantly impaired in the PD compared to the OA group. The PD group preformed significantly worse across all gait and postural sway tasks. In PD, SAI significantly correlated with single-task foot strike angle and stride length variability, sway area, and jerkiness of sway in the coronal and sagittal planes. In OAs, SAI significantly related to single-task gait speed and stride length, dual-task stride length, and immediate recall (memory domain). No relationship among mobility, cognition, and SAI was observed. CONCLUSIONS: Impaired SAI related to slower gait in OA and to increased gait variability and postural sway in people with PD, all of which have been shown to be related to increased fall risk.

Cerebrospinal Fluid MicroRNA Changes in Cognitively Normal Veterans With a History of Deployment-Associated Mild Traumatic Brain Injury.

A history of traumatic brain injury (TBI) increases the odds of developing Alzheimer's disease (AD). The long latent period between injury and dementia makes it difficult to study molecular changes initiated by TBI that may increase the risk of developing AD. MicroRNA (miRNA) levels are altered in TBI at acute times post-injury (<4 weeks), and in AD. We hypothesized that miRNA levels in cerebrospinal fluid (CSF) following TBI in veterans may be indicative of increased risk for developing AD. Our population of interest is cognitively normal veterans with a history of one or more mild TBI (mTBI) at a chronic time following TBI. We measured miRNA levels in CSF from three groups of participants: (1) community controls with no lifetime history of TBI (ComC); (2) deployed Iraq/Afghanistan veterans with no lifetime history of TBI (DepC), and (3) deployed Iraq/Afghanistan veterans with a history of repetitive blast mTBI (DepTBI). CSF samples were collected at the baseline visit in a longitudinal, multimodal assessment of Gulf War veterans, and represent a heterogenous group of male veterans and community controls. The average time since the last blast mTBI experienced was 4.7 ± 2.2 years [1.5 - 11.5]. Statistical analysis of TaqManTM miRNA array data revealed 18 miRNAs with significant differential expression in the group comparisons: 10 between DepTBI and ComC, 7 between DepC and ComC, and 8 between DepTBI and DepC. We also identified 8 miRNAs with significant differential detection in the group comparisons: 5 in DepTBI vs. ComC, 3 in DepC vs. ComC, and 2 in DepTBI vs. DepC. When we applied our previously developed multivariable dependence analysis, we found 13 miRNAs (6 of which are altered in levels or detection) that show dependencies with participant phenotypes, e.g., ApoE. Target prediction and pathway analysis with miRNAs differentially expressed in DepTBI vs. either DepC or ComC identified canonical pathways highly relevant to TBI including senescence and ephrin receptor signaling, respectively. This study shows that both TBI and deployment result in persistent changes in CSF miRNA levels that are relevant to known miRNA-mediated AD pathology, and which may reflect early events in AD.

Guidance for biostatisticians on their essential contributions to clinical and translational research protocol review.

Rigorous scientific review of research protocols is critical to making funding decisions, and to the protection of both human and non-human research participants. Given the increasing complexity of research designs and data analysis methods, quantitative experts, such as biostatisticians, play an essential role in evaluating the rigor and reproducibility of proposed methods. However, there is a common misconception that a statistician's input is relevant only to sample size/power and statistical analysis sections of a protocol. The comprehensive nature of a biostatistical review coupled with limited guidance on key components of protocol review motived this work. Members of the Biostatistics, Epidemiology, and Research Design Special Interest Group of the Association for Clinical and Translational Science used a consensus approach to identify the elements of research protocols that a biostatistician should consider in a review, and provide specific guidance on how each element should be reviewed. We present the resulting review framework as an educational tool and guideline for biostatisticians navigating review boards and panels. We briefly describe the approach to developing the framework, and we provide a comprehensive checklist and guidance on review of each protocol element. We posit that the biostatistical reviewer, through their breadth of engagement across multiple disciplines and experience with a range of research designs, can and should contribute significantly beyond review of the statistical analysis plan and sample size justification. Through careful scientific review, we hope to prevent excess resource expenditure and risk to humans and animals on poorly planned studies.

Comprehensive maternal serum proteomic profiles of preclinical and clinical preeclampsia.

We systematically characterized maternal serum proteome in women with clinical preeclampsia (PE) and asymptomatic women in early pregnancy that subsequently developed PE. Clinical PE cohort comprised 30 patients with mild PE, 30 with severe PE, and 58 normotensive women. Preclinical PE cohort included 149 women whose serum samples were collected at 8-14 gestational weeks and in whom 30 women later developed mild and 40 severe PE. Serum proteome was analyzed and enzyme-linked immunosorbent assays were used for protein quantification. In Clinical PE, fibronectin, pappalysin-2, choriogonadotropin-beta, apolipoprotein C-III, cystatin-C, vascular endothelial growth factor receptor-1, and endoglin were more abundant compared to normotensive women. In preclinical PE, differently expressed proteins included placental, vascular, transport, matrix, and acute phase proteins. Angiogenic and antiangiogenic proteins were not significant. We conclude that placental and antiangiogenic proteins are abundant in clinical PE. In preclinical PE, proteomic profile is distinct and different from that in clinical PE.

Association between sex steroids and cognition in elderly men.

OBJECTIVE: To examine the association of cognitive function with sex steroid and sex hormone binding globulin (SHBG) levels among elderly men. DESIGN: Prospective cohort study, The Osteoporotic Fractures in Men Study (MrOS), consisting of 5995 US community dwelling men of 65 years or older. PATIENTS: One thousand six hundred and two men were chosen randomly from MrOS cohort for sex steroid level measurements by Mass Spectrometry (MS) at baseline. Two thousand six hundred and twenty-three MrOS participants with sex steroids measured using RIA were also examined. MEASUREMENTS: Baseline and follow-up (4.5 years later) performance on two cognitive tests: Trails B (executive function and motor speed) and 3MS (global cognitive function). Baseline total testosterone and oestradiol were measured by MS. Free testosterone (free-T) and free oestradiol (free-E) were calculated. SHBG was measured by radioimmunoassay. Data were analysed using linear regression. RESULTS: Baseline free-T and free-E levels were not associated with cognitive performance or change in cognition, following adjustment for age, education, race, health status and alcohol use. Baseline SHBG levels were inversely associated with follow-up trails B (P = 0.03) and 3MS performance (P = 0.02). Higher SHBG was associated with an increased risk of cognitive decline. Total sex steroid levels were not associated with cognitive performance. CONCLUSIONS: Despite large numbers of participants and rigorous sex steroid measurements, we did not observe an association between cognition and either testosterone or oestradiol levels. We conclude that endogenous sex steroids in the normal range are not related to executive function or global cognitive function in elderly men. High SHBG deserves further examination as a risk factor for cognitive decline.

Insights into the multifactorial nature of preterm birth: proteomic profiling of the maternal serum glycoproteome and maternal serum peptidome among women in preterm labor.

OBJECTIVE: The purpose of this study was to identify peptide classifiers that predict spontaneous preterm birth (SPTB) among women in preterm labor (PTL) and to demonstrate specific protein pathways that are activated in PTL. STUDY DESIGN: Serum from 110 women with PTL between 20 weeks and 33 weeks 6 days of gestation was subjected to glycoprotein purification, matrix-assisted laser desorption ionization time-of-flight mass spectrometry peptide profiling, 2-dimensional liquid chromatography tandem mass spectrometry, and pathway analysis. Women were divided into 2 groups: delivery at <34 weeks' gestation (SPTB group) and delivery at > or =34 weeks' gestation (PTL group). RESULTS: Twenty-three peptide masses were identified that discriminated PTL from SPTB in 97% of cases. Fifty-two proteins were present differentially between PTL and SPTB; 48 of 52 proteins were classified into 1 of 4 functional pathways that were involved with PTL: (1) complement/coagulation cascade, (2) inflammation/immune response, (3) fetal-placental development, and (4) extracellular matrix proteins. CONCLUSION: Among women in PTL, proteomic analysis of serum peptides and glycoproteins classifies women who will deliver preterm and identifies specific protein pathways at work among individuals with "idiopathic" PTL.

Noninvasive diagnosis of intraamniotic infection: proteomic biomarkers in vaginal fluid.

OBJECTIVE: We analyzed the vaginal fluid proteome to identify biomarkers of intraamniotic infection among women in preterm labor. STUDY DESIGN: Proteome analysis was performed on vaginal fluid specimens from women with preterm labor, using multidimensional liquid chromatography, tandem mass spectrometry, and label-free quantification. Enzyme immunoassays were used to quantify candidate proteins. Classification accuracy for intraamniotic infection (positive amniotic fluid bacterial culture and/or interleukin-6 >2 ng/mL) was evaluated using receiver-operator characteristic curves obtained by logistic regression. RESULTS: Of 170 subjects, 30 (18%) had intraamniotic infection. Vaginal fluid proteome analysis revealed 338 unique proteins. Label-free quantification identified 15 proteins differentially expressed in intraamniotic infection, including acute-phase reactants, immune modulators, high-abundance amniotic fluid proteins and extracellular matrix-signaling factors; these findings were confirmed by enzyme immunoassay. A multi-analyte algorithm showed accurate classification of intraamniotic infection. CONCLUSION: Vaginal fluid proteome analyses identified proteins capable of discriminating between patients with and without intraamniotic infection.

Chronic opioid therapy and preventive services in rural primary care: an Oregon rural practice-based research network study.

PURPOSE: For clinicians, using opioid therapy for chronic noncancer pain (CNCP) often gives rise to a conflict between treating their patients' pain and fears of addiction, diversion of medication, or legal action. Consequent stresses on clinical encounters might adversely affect some elements of clinical care. We evaluated a possible association between chronic opioid therapy (COT) for CNCP and receipt of various preventive services. METHODS: We conducted a retrospective cohort study in 7 primary care clinics within the Oregon Rural Practice-based Research Network (ORPRN). Using medical records of 704 patients, aged 35 to 85 years, seen during a 3-year period, we compared the receipt of 4 preventive services between patients on COT for CNCP and patients not on chronic opioid therapy (non-COT). We used multivariate log-binomial regression analyses to estimate the relative risk of receipt of each preventive service. RESULTS: After adjustment for plausible confounders, we found that patients using COT had a statistically significantly lower relative risk (RR) of receipt of cervical cancer screening (RR = 0.60; 95% confidence interval [CI], 0.47-0.76) and colorectal cancer screening (RR = 0.42; 95% CI, 0.22-0.80) when compared with non-COT patients. The RR was reduced, without statistical significance, for lipid screening (RR = 0.77; 95% CI, 0.54-1.10), and not notably reduced for smoking cessation counseling (RR = 0.95; 95% CI, 0.78-1.15). CONCLUSIONS: Patients using COT for CNCP were less likely to receive some preventive services. Research is needed to better understand barriers to and improved methods for providing preventive services for these patients.

Association of Palliative Care Use and Setting With Health-care Utilization and Quality of Care at the End of Life Among Patients With Advanced Lung Cancer.

BACKGROUND: Palliative care is associated with improved survival and quality of life among patients with lung cancer; however, its influence on health-care utilization and quality of care is unclear. RESEARCH QUESTION: Is palliative care, and the setting in which it occurs, associated with health-care resource utilization and quality of care among patients with advanced lung cancer? STUDY DESIGN AND METHODS: This was a retrospective cohort study of 23,142 patients with stage IIIB/IV lung cancer in the Veterans Affairs HealthCare System between 2007 and 2013. Exposures included the receipt of specialist-delivered palliative care, and the setting of the initial palliative care encounter (inpatient or outpatient) received after cancer diagnosis. Primary outcomes included rates of ED visits, along with rates of hospitalization and odds of ICU admission within the last 30 days of life. Secondary outcomes included any health-care utilization (ED, hospital, or ICU) related to chemotherapy toxicity. We used propensity score methods to perform Poisson and logistic regression modeling. RESULTS: Among the 23,142 patients, 57% received palliative care, and 36% of initial palliative care encounters were outpatient. Compared with no palliative care, initial palliative care encounter in the outpatient setting was associated with reduced rates of ED visits (adjusted incidence rate ratio [aIRR], 0.86; 95% CI, 0.77-0.96) and hospitalizations in the last 30 days of life (aIRR, 0.64; 95% CI, 0.59-0.70). Initial palliative care encounters in both inpatient (adjusted OR [aOR], 0.63; 95% CI, 0.53-0.75) and outpatient (aOR, 0.42; 95% CI, 0.35-0.52) settings were associated with reduced odds of ICU admission in the last 30 days of life. Palliative care was also associated with reduced health-care utilization related to chemotherapy toxicity (aOR, 0.88; 95% CI, 0.82-0.95). INTERPRETATION: Palliative care (particularly in outpatient settings) is associated with reduced health-care utilization at the end of life and may improve the quality of care among patients with advanced lung cancer. These findings support the role of palliative care as an important component of comprehensive cancer care and highlight the potential benefits of outpatient palliative care services.